Neurotrophin-3 (NT-3) and anti-NogoA have shown promise in regenerative strategies after spinal cord injury; however, conventional methods for localized release to the injured spinal cord are either prone to infection or not suitable for sustained release. To address these issues, we have designed a composite drug delivery system that is comprised of poly(lactic-co-glycolic acid) (PLGA) nanoparticles dispersed in an injectable hydrogel of hyaluronan and methyl cellulose (HAMC). Achieving sustained and bioactive protein release from PLGA particles is a known challenge; consequently, we studied the effects of processing parameters and excipient selection on protein release, stability, and bioactivity. We found that embedding PLGA nanoparticles in HAMC results in more linear drug release due to the formation of a diffusion-limiting layer of methyl cellulose on the particle surface. Co-encapsulated MgCO3 was able to significantly improve NT-3 bioactivity, while trehalose + hyaluronan was able to improve anti-NogoA bioactivity and release.

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Calcium phosphate spheres as biomaterials have been attracting attention in recent years. Calcium phosphate occurs naturally in bone, and a hollow structure could be advantageous for drug loading and release. The combination of a calcium phosphate chemistry and a spherical-hollow structure could be an optimal strategy for specific biomaterial applications, e.g., certain dental and drug-delivery applications. The focus of this thesis is on the synthesis, formation mechanism and applications of hollow, spherical calcium phosphate particles. First, the thesis describes two methods for the synthesis of calcium phosphate (CaP) spherical particles. The first method involves synthesis of hollow calcium phosphate spherical particles via a supersaturated buffer solution based on a previous study. It was utilised to prepare spheres for applications in drug delivery and dentistry. The second method was developed to explain the mechanism of formation of hollow calcium phosphate spheres. It aimed at revealing the particular function of magnesium in the formation of spherical particles. With the use of this modified method, it could be concluded that the only ions active in the formation of CaP spherical particles are calcium ions, phosphate ions and magnesium ions. Compared with the thermodynamics of micellisation, a new model, called three ions virtual micelle effect, was developed to explain the mechanism of the Mg function. Following this mechanism, a series of spherical particles of other compositions were explored. These spherical particles included strontium phosphate, barium phosphate, calcium fluoride, strontium fluoride and barium fluoride. In this thesis, CaP spheres were studied for the controlled delivery of active ingredients and as active agent for tooth remineralisation. The first investigated application was to control the release of vancomycin from Poly(methyl methacrylate) (PMMA) cement via strontium-doped CaP spheres (SCPS). The results showed that incorporation of CaP spheres into PMMA could enhance antibiotic release while maintaining the mechanical strength. The second application was to control hydrogen peroxide (HP) release from two bleaching gel, in which CP-loaded CaP spheres were the active ingredient. One gel with low HP concentration was developed as an at-home bleaching gel, and one with high HP concentration was developed as an in-office bleaching gel. The results showed that CaP spheres would give a controlled release of peroxide and thus have a potential to increase the efficacy of the bleaching. The third application was to investigate the potential for an anti-sensitivity effect of the spheres, as active agents in toothpaste. We studied the tooth tubules occlusion and the remineralisation effect of CaP spheres. After 7 days of application, the open dentin tubules and surface were fully covered by a newly formed apatite layer, demonstrating the remineralisation potential of the spheres.

Thesis in theoretical part provides an overview of oral drugs in the biopharmaceutical point of view. It describes the main difficulties of this application route and presents selected facts about new approaches to improve the bioavailability of poorly absorbable substances. These approaches, in recent years, also use nanofiber membranes. The experimental part focuses on the in vitro evaluation of diamine delivery from nanofiber membranes in vehicle buffered at pH 7.4. The tested membranes contain the active substance in three graduated concentrations (20%, 30% and 40%), and specifically differ in basic weight. To evaluate the delivery the fluxes of diamine witin the first linear section of delivery are used, the percentage of substance released within 60 minutes was used to the evaluation of releasable proportion of diamine. Determination of diamine was performed by HPLC. The release of nearly all releasable diamine amounts were always obtained in 15 minutes from the beginning of release. The release rate of the diamine from nanofiber membranes is high. Important, however, is the finding that the rate of drug release is not probably significantly dependent on the drug concentration in the nanofiber membrane, but it is significantly influenced by the basic weight of membranes. The variability...

A theoretical part of the diploma thesis describes solubility, classification of solubility and ways of influencing of solubility, and it gives a detailed summary of naproxen as the drug further used and evaluated in in vitro experiments for drug release. An experimental section is focused to in vitro release of naproxen from nanofibre membranes produced by electrospinning with regard to the possibility of the use of layering. At both layered and non-layered nanofibre membranes of three different naproxen concentrations (e.g. 5%, 15% and 30% by weight) the drug release amounts within 5 minutes were from 10 to 90 percent of total amounts. An overal percentage of naproxen released in 60 minutes was always about 100 % of the total drug loaded in the nanomembranes. The nanofibre membranes layered with the glycerol and propylene glycol were of the same profiles as with non-layered membranes.

Infektionen medizinscher Titanoberflächen stellen ein aktuelles Problem in der rekonstruktiven Medizin dar. Dabei wird oft versucht, diesem Problem mit systemischer Antibiotikaanwendung zu begegnen, die jedoch Resistenzentstehung begünstigt und am Ort der Infektion nur einen oft unzureichenden Wirkspiegel ermöglicht. Eine mögliche Verbesserung wir hierbei in lokaler Wirkstofffreisetzung gesehen. Gegenstand dieser Arbeit war die Modifikation medizinischer Titanoberflächen mittels Anodisierung in fluoridhaltigen Elektrolyten und die Abschätzung ihres Potentials hinsichtlich der Einlagerung und der Freisetzung ausgewählter antibakteriell wirksamer Substanzen. Durch die Anodisierung der Titanoberflächen konnten Titannanotubes aus Titanoxiden mit Röhrenlängen von bis zu 6,54 m und Röhrendurchmessern von bis zu 160 nm erzeugt werden. Als Modellwirkstoffe wurden das noch heute als Reserveantibiotikum gegen manche Problemkeime geltende Chemotherapeutikum Vancomycin, sowie Silber als Element mit breiter antibakterieller Wirkung, verwendet. Es konnte gezeigt werden, dass durch die Oberflächenvergrößerung, die sich aus der Entstehung von nanotubeförmigem Titanoxid ergab, im Vergleich zu nicht anodisierten Referenzproben um bis zu 447 % mehr Wirkstoff eingelagert werden konnte. In der Freisetzungskinetik von Vancomycin zeigten sich oberflächenabhängig deutliche Unterschiede. Dabei setzten Titanoberflächen, die in einem Elektrolyten auf Wasserbasis anodisiert worden waren, den adsorbierten Wirkstoff schneller frei als die Referenzproben, während das Vancomycin auf Oberflächen, die in einem Elektrolyten auf Ethylenglycolbasis modifiziert worden waren, deutlich retardiert über einen Zeitraum von circa 305 Tagen freigesetzt wurde. Des weiteren wurde Silber in Proben eingelagert, die in einem Elektrolyten auf Wasserbasis anodisiert worden waren. Auch für Silber resultierte eine deutliche Steigerung der Gesamtmenge des adsorbierten Wirkstoffs um bis zu 229 %. Dabei war seine Freisetzung, verglichen mit der Referenzprobe, deutlich verzögert. Durch die Anodisierung der Titanproben in fluoridhaltigen Elektrolyten konnten Oberflächen erzeugt werden, die entsprechend ihrer Morphologie verschiedene Wirkstoffbeladungen und Freisetzungskinetiken ermöglichen. Hinsichtlich der unterschiedlichen Anforderungen in der klinischen Medizin nach Abgabemenge und Abgabekinetik antibakteriell wirksamer Substanzen zur postoperativen Infektionsprävention offerieren diese Oberflächenmodifikationen ein hohes Potential für die Erzeugung schnell verfügbarer und kostengünstiger Drug-Release-Systeme. / Infection of medical titanium surfaces is one important problem in modern medicine, especially orthepedics and dentistry. In the present work titanium surfaces were modified by anodisation. Titanium nanotube formations of different shape were obtained. These surfaces were modified with example drugs (vancomycin and silver ions) for drug-release. Drug-release was measured and compered.

<p>New smart drugs demand new smart drug delivery systems and also new smart analysis methods for the drug delivery process and material characterization. This thesis contributes to the field by introducing a new electrodynamic approach for studying the drug diffusion proc-esses as well as the formation of a new type of drug delivery systems, the so called mesoporous nano excipients.</p><p>Drug diffusion processes from different pharmaceutical materials were examined. The transport of charged drug substances was investigated by electrodynamic methods; either as a release process governed by diffusion using the alternating ionic current method or by applying a voltage, sinusoidal or dc, to force the drug ions to move in an electric field.</p><p>Temperature-dependent drug release from microcrystalline cellulose tablets was examined in order to extract information about the diffu-sion process. Percolation theory was also employed to binary mixtures of an insoluble and electrically insulating matrix material together with a soluble and ionic conducting drug. Further, dielectric spectros-copy was proven to be a powerful method for examining the state of vesicle formation of drug and surfactant molecules in a carbopol gel. Finally, a new potential class of pharmaceutical materials were exam-ined, namely the AMS-n mesoporous materials, showing that the al-ternating ionic current method is powerful both in the study of the synthesis of and in the release process from these. </p>

Stem cell based therapy has the potential to treat several severe diseases; Parkinson’s disease is one well- known example. Transplantation of stem cell derived cells into animal models is unfortunately often associated with tumour formation or- uncontrolled growth of the transplanted cells. One strategy to suppress this tumour formation might be to induce differentiation of these cells, which in turn would prevent them from dividing.   Neuroblastoma tumors are known to demonstrate the complete transition from an undifferentiated state to a completely harmful, differentiated appearance and derived cells can be used as a model for cell differentiation and tumor suppression.   In this Master Thesis’s the conducting polymers PEDOT and PPy, that upon formation can be doped with biologically active compounds which in- turn can be released in a controlled manner through electrical stimulation, were formed together with various drugs (e.g. Methotrexate and Mycophenolic Acid), here shown to have effect on Neuroblastoma cells. Neuroblastoma- derived cell line SH- SY5Y was used as a model system for neuronal differentiation and tumour inhibition. Release profiles of neuroblastoma active drugs following electrical stimulation were evaluated and the effects from electrochemical processes on simultaneously growing SH- SY5Y cells were investigated.   The methods to deposit and release the drugs were based on electropolymerization and electrochemically controlled release, respectively. Controlled release of various drugs and compounds was monitored using Vis- and UV- spectroscopy and on some occasions using HPLC.   The electrochemically controlled release of a biologically inactive compound that can be used as a negative control for electrochemical release in future experiments was shown and that resulting electrochemical processes have negative effects on neuroblastoma cell growth.